Headache for Addex as migraine study is pulled

Shares in Addex Pharmaceuticals have been suspended this morning after the Switzerland-headquartered firm said it is terminating a mid-stage trial of its investigational migraine drug due to liver problems.

ADX10059 was being studied in a 240-patient Phase IIb trial in people who suffer from three or more migraine attacks per month. However, Addex says that routine safety monitoring of blinded data in the study has revealed “an incidence of abnormalities of liver function tests that is higher than expected in this population”.

These abnormalities are apparent from day 28 of dosing, the Geneva-based company says, but “the incidence and severity appear to increase progressively with increasing duration of participation’ in the study. Addex went on to say that despite the fact the treatment allocation remains blinded, it is of the opinion “that the risk-to-benefit profile of the drug observed in the study is not sufficiently favourable to justify continuation of the trial”.

The SIX Swiss Exchange said Addex has asked for its shares to be suspended from trading today, as the stock had been indicated to fall some 30% at opening.

Chief executive Vincent Mutel said that “this is an unfortunate and unexpected development". He added that the firm is working to “rapidly understand the relationship of the liver function abnormalities to the treatment and the implications for development of ADX10059 in migraine prevention and other indications”.

It is a particularly hard blow, seeing as how Addex noted just a month ago that a separate Phase IIb trial of the drug, a first-in-class reflux inhibitor that works by reducing activation of the metabotropic glutamate receptor 5, showed that it increased the number of symptom-free days as a monotherapy in patients with gastroesophageal reflux disease and no liver function abnormalities were seen. Also, enrolment has been completed in the second trial of ADX10059 in GERD patients as an add-on therapy in patients who are partial responders to proton pump inhibitors, the standard therapy.

Addex also noted that mGluR5 inhibitors have achieved clinical proof of concept in patients with Parkinson’s disease levodopa-induced dyskinesia and generalised anxiety disorder. However their potential may now be difficult to sell to partners following the liver problem in the migraine trial.

Earlier this month, Addex extended a potentially-lucrative Parkinson’s disease collaboration it has with Merck & Co.